Lamivudine Chemical formula
Synonyms: 3TC; (−)-2′-Deoxy-3′-thiacytidine; GR-109714X; Lamivudiini; Lamivudin; Lamivudina; Lamivudinum; Lamiwudyna; Lavmivudin. (−)-1-[(2R,5S)-2-(Hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.
Cyrillic synonym: Ламивудин.

💊 Chemical information

Chemical formula: C8H11N3O3S = 229.3.
CAS — 131086-21-0; 134678-17-4.
ATC — J05AF05.
ATC Vet — QJ05AF05.


In Eur. and US.

Ph. Eur. 6.2

(Lamivudine). A white or almost white powder. It exhibits polymorphism. Soluble in water, slightly soluble in alcohol; sparingly soluble in methyl alcohol. Protect from light.

USP 31

( Lamivudine). A white to off-white solid. Soluble in water. Protect from light.

💊 Adverse Effects

Adverse effects commonly associated with lamivudine either as monotherapy or with other antiretrovirals for the treatment of HIV include abdominal pain, nausea, vomiting, diarrhoea, headache, fever, rash, alopecia, malaise, insomnia, cough, nasal symptoms, arthralgia, and musculoskeletal pain. There have also been reports of pancreatitis, anaemia, neutropenia, and thrombocytopenia. Increases in liver enzymes and serum amylase may occur. Lactic acidosis, usually associated with severe hepatomegaly and steatosis, has been reported during treatment with nucleoside reverse transcriptase inhibitors. Immune reconstitution syndrome (an inflammatory immune response resulting in clinical deterioration) has been reported during the initial phase of treatment with combination antiretroviral therapy, including lamivudine, in HIV-infected patients with severe immune deficiency. Accumulation or redistribution of body fat (lipodystrophy) including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have been seen in patients receiving antiretroviral therapy, including lamivudine. Metabolic abnormalities such as hypertriglyceridaemia, hypercholesterolaemia, insulin resistance, hyperglycaemia, and hyperlactataemia have also been reported. NRTIs have also been associated with mitochondrial dysfunction manifesting as abnormal behaviour, anaemia, convulsions, hyperlipasaemia, hypertonia, and neutropenia. Elevated creatine phosphokinase, myalgia, myositis, and rarely rhabdomyolysis have been reported, particularly when nucleoside analogues have been given with HIV-protease inhibitors. Osteonecrosis has been reported, particularly in patients with advanced HIV disease or long-term exposure to combination antiretroviral therapy. For further information on adverse effects associated with NRTIs see Zidovudine. Patients taking a lower dose of lamivudine for the treatment of chronic hepatitis B often have abdominal discomfort and pain, diarrhoea, fatigue, headache, nausea, malaise, respiratory-tract infections, and vomiting. The most frequently reported laboratory abnormalities are elevated creatine phosphokinase, increases in serum lipase, and raised liver enzymes, in particular alanine aminotransferase. There have been rare reports of lactic acidosis, pancreatitis, and muscle disorders such as cramps, myalgia, and rhabdomyolysis.

Effects on the blood.

Although anaemia associated with lamivudine usually occurs when it is used with zidovudine, there has been a report1 of severe anaemia in a 62-year-old HIV-infected man given lamivudine alone.
1. Weitzel T, et al. Severe anaemia as a newly recognized side-effect caused by lamivudine. AIDS 1999; 13: 2309–11.

Effects on the hair.

Hair loss was associated with lamivudine treatment in 5 patients.1
1. Fong IW. Hair loss associated with lamivudine. Lancet 1994; 344: 1702.

Effects on the nervous system.

Exacerbation of peripheral neuropathy has been reported in a patient after substitution of lamivudine for zalcitabine.1
1. Cupler EJ, Dalakas MC. Exacerbation of peripheral neuropathy by lamivudine. Lancet 1995; 345: 460–1.


Angioedema, urticaria, and anaphylactoid reaction occurred in a patient 30 minutes after receiving the first dose of lamivudine.1
1. Kainer MA, Mijch A. Anaphylactoid reaction, angioedema, and urticaria associated with lamivudine. Lancet 1996; 348: 1519.

💊 Precautions

Lamivudine therapy should be stopped in patients who develop abdominal pain, nausea, or vomiting or with abnormal biochemical test results until pancreatitis has been excluded. Treatment with lamivudine may be associated with lactic acidosis and should be stopped if there is a rapid increase in aminotransferase concentrations, progressive hepatomegaly, or metabolic or lactic acidosis of unknown aetiology. Lamivudine should be used with caution in patients with hepatomegaly or other risk factors for hepatic disease. Patients co-infected with HIV and chronic hepatitis B or C and treated with combination antiretroviral therapy are at increased risk for severe and potentially fatal hepatic adverse events. In patients with chronic hepatitis B, there is a risk of rebound hepatitis when lamivudine is stopped, and liver function should be monitored in such patients. The possibility of HIV infection should be excluded before beginning lamivudine therapy for hepatitis B, since the lower doses used to treat the latter may permit the development of lamivudine-resistant strains of HIV. Dosage reduction may be necessary in patients with impaired renal function.

💊 Interactions

The renal excretion of lamivudine may be inhibited by other drugs mainly eliminated by active renal secretion, for example trimethoprim. Usual prophylactic doses of trimethoprim are unlikely to necessitate reductions in lamivudine dosage unless the patient has renal impairment, but the co-administration of lamivudine with the high doses of trimethoprim (as co-trimoxazole) used in pneumocystis pneumonia and toxoplasmosis should be avoided. Although there is usually no clinically significant interaction with zidovudine, severe anaemia has occasionally been reported in patients given lamivudine with zidovudine. Lamivudine may antagonise the antiviral action of zalcitabine and the two drugs should not be used together. Once daily triple nucleoside regimens of lamivudine and tenofovir with either abacavir or didanosine are associated with a high level of treatment failure and of emergence of resistance, and should be avoided.


For a possible interaction between phenylpropanolamine and antiretrovirals, see Stavudine.

💊 Antiviral Action

Lamivudine is converted intracellularly in stages to the triphosphate. This triphosphate halts the DNA synthesis of retroviruses, including HIV, through competitive inhibition of reverse transcriptase and incorporation into viral DNA. Lamivudine is also active against hepatitis B virus. Resistance to lamivudine has been reported in isolates of HIV and hepatitis B virus.

💊 Pharmacokinetics

Lamivudine is rapidly absorbed after oral doses and peak plasma concentrations are achieved in about 1 hour. Absorption is delayed, but not reduced, by ingestion with food. Bioavailability is between 80 and 87%. Binding to plasma protein is reported to be up to 36%. Lamivudine crosses the blood-brain barrier with a ratio of CSF to serum concentrations of about 0.12. It crosses the placenta and is distributed into breast milk. Lamivudine is metabolised intracellularly to the active antiviral triphosphate. Hepatic metabolism is low and it is cleared mainly unchanged by active renal excretion. An elimination half-life of 5 to 7 hours has been reported after a single dose.
1. Mueller BU, et al. Serum and cerebrospinal fluid pharmacokinetics of intravenous and oral lamivudine in human immunodeficiency virus-infected children. Antimicrob Agents Chemother 1998; 42: 3187–92
2. Johnson MA, et al. Clinical pharmacokinetics of lamivudine. Clin Pharmacokinet 1999; 36: 41–66
3. Bruno R, et al. Comparison of the plasma pharmacokinetics of lamivudine during twice and once daily administration in patients with HIV. Clin Pharmacokinet 2001; 40: 695–700
4. Treatment with lamivudine plus zidovudine has produced better responses than either drug alone in antiretroviral-naive patients,6,7 and has produced additional responses in antiretroviral-experienced patients,8,9 with little additional toxicity. The addition of lamivudine to existing antiretroviral therapy was reported to slow the progression of the disease and improve survival,10 and treatment with lamivudine, indinavir, and nevirapine produced beneficial responses in patients who had previously failed on combined nucleoside analogue therapy.11 Clinically useful CNS concentrations of lamivudine were achieved in patients with HIV infection given combination therapy with lamivudine and zidovudine or stavudine.12 Lamivudine is also used in prophylactic regimens after occupational exposure to HIV infection and has been tried for reducing vertical transmission from mother to neonate.13,14
1. Anonymous. Lamivudine: impressive benefits in combination with zidovudine. WHO Drug Inf 1996; 10: 5–7
2. Wainberg MA, et al. Development of HIV-1 resistance to (−)2′deoxy-3′-thiacytidine in patients with AIDS or advanced AIDSrelated complex. AIDS 1995; 9: 351–7
3. Ingrand D, et al. Phase I/II study of 3TC (lamivudine) in HIVpositive, asymptomatic or mild AIDS-related complex patients: sustained reduction in viral markers. AIDS 1995; 9: 1323–9
4. Larder BA, et al. Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 1995; 269: 696–9
5. Miller V, et al. Dual resistance to zidovudine and lamivudine in patients treated with zidovudine-lamivudine combination therapy: association with therapeutic failure. J Infect Dis 1998; 177: 1521–32
6. Eron JJ, et al. Treatment with lamivudine, zidovudine, or both in HIV-positive patients with 200 to 500 CD4+ cells per cubic millimeter. N Engl J Med 1995; 333: 1662–9
7. Katlama C, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients: a randomized controlled comparison with zidovudine monotherapy. JAMA 1996; 276: 118–25
8. Staszewski S, et al. Safety and efficacy of lamivudine-zidovudine combination therapy in zidovudine-experienced patients: a randomized controlled comparison with zidovudine monotherapy. JAMA 1996; 276: 111–17
9. Bartlett JA, et al. Lamivudine plus zidovudine compared with zalcitabine plus zidovudine in patients with HIV infection: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996; 125: 161–72
10. CAESAR Coordinating Committee. Randomised trial of addition of lamivudine or lamivudine plus loviride to zidovudinecontaining regimens for patients with HIV-1 infection: the CAESAR trial. Lancet 1997; 349: 1413–21
11. Harris M, et al. A pilot study of nevirapine, indinavir, and lamivudine among patients with advanced human immunodeficiency virus disease who have had failure of combination nucleoside therapy. J Infect Dis 1998; 177: 1514–20
12. Foudraine NA, et al. Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine. Lancet 1998; 351: 1547–51
13. Mandelbrot L, et al. Lamivudine-zidovudine combination for prevention of maternal-infant transmission of HIV-1. JAMA 2001; 285: 2083–93
14. The Petra Study Team. Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial. Lancet 2002; 359: 1178–86.

💊 Preparations

Proprietary Preparations

Arg.: 3TC; Amilitrap; Birvac†; Ganvirel; Heptodine; Hivirux†; Imunoxa; Kess; Lamibergen; Lamilea; Oralmuv; Ultraviral; Vuclodir; Zeffix†; Austral.: 3TC; Zeffix; Austria: Epivir; Zeffix; Belg.: Epivir; Zeffix; Braz.: Epivir; Lami; Vudirax; Zeffix†; Canad.: 3TC; Heptovir; Chile: 3TC/Epivir; Cz.: Epivir; Zeffix; Denm.: Epivir; Zeffix; Fin.: Epivir; Zeffix; Fr.: Epivir; Zeffix; Ger.: Epivir; Kivexa; Zeffix; Gr.: Epivir; Zeffix; Hong Kong: 3TC; Zeffix; Hung.: Epivir; Zeffix; India: Ladiwin; Lamda; Lamidac; Lamirex†; Lamivir; Indon.: 3TC; 3TC-HBV; Irl.: Epivir; Zeffix; Israel: Epivir; Zeffix; Ital.: Epivir; Zeffix; Jpn: Epivir†; Malaysia: 3TC; Zeffix; Mex.: 3TC; Neth.: Epivir; Zeffix; Norw.: Epivir; Zeffix; NZ: 3TC; Zeffix; Philipp.: Zeffix; Pol.: Epivir; Zeffix; Port.: Epivir; Zeffix; Rus.: Epivir (Эпивир); Zeffix (Зеффикс); S.Afr.: 3TC; Singapore: Epivir; Zeffix; Spain: Epivir; Zeffix; Swed.: Epivir; Zeffix; Switz.: 3TC; Zeffix; Thai.: Epivir; Zeffix; Turk.: Epivir; Zeffix; UK: Epivir; Zeffix; USA: Epivir; Venez.: Epivir; Heptodine†; Lamivir. Multi-ingredient: Arg.: 3TC Complex; 3TC/AZT; Ganvirel Duo; Hivirux Complex†; Imunoxa Complex; Kess Complex; Kivexa; Muvidina; Tricivir; Trivudin; Ultraviral Duo; Zetavudin; Austral.: Combivir; Kivexa; Trizivir; Austria: Combivir; Trizivir; Belg.: Combivir; Kivexa; Trizivir; Braz.: Biovir; Duovir†; Vir-Complex†; Zidolam; Canad.: Combivir; Kivexa; Trizivir; Chile: Combivir; Kivexa; Tricivir; Cz.: Combivir; Kivexa; Trizivir; Denm.: Combivir; Kivexa; Trizivir; Fin.: Combivir; Kivexa; Trizivir; Fr.: Combivir; Kivexa; Trizivir; Ger.: Combivir; Trizivir; Gr.: Combivir; Kivexa; Trizivir; Hong Kong: Combivir; Trizivir; Hung.: Combivir; Kivexa; Trizivir; India: Combirex†; Duovir; Duovir N; Lamda-Z; Lamivir S; Lamuzid; Odivir Kit; Triomune; Irl.: Combivir; Kivexa; Trizivir; Israel: Combivir; Trizivir; Ital.: Combivir; Kivexa; Trizivir; Malaysia: Combivir; Mex.: Combivir; Kivexa; Trizivir; Neth.: Combivir; Kivexa; Trizivir; Norw.: Combivir; Kivexa; Trizivir; NZ: Combivir; Kivexa; Trizivir; Philipp.: Combivir; Pol.: Combivir; Kivexa; Trizivir; Port.: Combivir; Kivexa; Trizivir; Rus.: Combivir (Комбивир); Trizivir (Тризивир); S.Afr.: Combivir; Duovir; Lamzid; Retrovir/3TC PostHIV Exposure†; Triomune; Trizivar; Singapore: Combivir; Trizivir†; Spain: Combivir; Kivexa; Trizivir; Swed.: Combivir; Kivexa; Trizivir; Switz.: Combivir; Trizivir; Thai.: Combid; Turk.: Combivir; UK: Combivir; Kivexa; Trizivir; USA: Combivir; Epzicom; Trizivir; Venez.: Combivir; Duovir; Triomune; Trizivir.
Published December 03, 2018.